Comparison of Human Leukocyte Antigen DR-DQ Disease Associations Found With Cervical Dysplasia and Invasive Cervical Carcinoma

• Published in: JNCI : Journal of the National Cancer Institute 1995-03, Vol.87 (6), p.427-436
• Main Authors: Apple, Raymond J., Becker, Thomas M., Wheeler, Cosette M., Erlich, Henry A.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; Cervical cancer; Cervical Intraepithelial Neoplasia - immunology; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; DNA Probes; DNA, Neoplasm; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Haplotypes; Hispanic Americans; HLA-DQ Antigens - blood; HLA-DR Antigens - blood; Humans; Medical research; Medical sciences; Neoplasm Invasiveness; Nucleic Acid Hybridization; Papillomaviridae; Polymerase Chain Reaction; Reproductive system; Tumors; Uterine Cervical Dysplasia - immunology; Uterine Cervical Dysplasia - virology; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/87.6.427

Background: Human leukocyte antigen (HLA) molecules, whose biological role is in the regulation of immune responses to foreign antigens and in discrimination of self from non-self antigens, are encoded by a series of closely linked genetic loci found on chromosome 6. Although the evidence for a link between HLA and cervical cancer has been controversial, it has been recently reported that certain HLA class II haplotypes (linked class II alleles) are positively associated with invasive cervical cancer, while other class II haplotypes are negatively associated or protective. Since HLA associations between human papillomavirus type 16 (HPV16)-mediated cancer cases and non-HPV16-mediated cancer cases have been found to be different, this suggests that specific HLA class II haplotypes may influence the immune response to HPV infection and may affect the risk of acquiring invasive cervical carcinoma. Purpose: This study was conducted to determine if the same HLA class II haplotypes that are associated with invasive cervical carcinoma are also associated with cervical dysplasia (pre-sumed precursors of invasive cervical cancer). Methods: We have examined HLA DR-DQ haplotypes among 128 Hispanic women from New Mexico with biopsy-confirmed cervical dysplasia in a case-control study using sensitive DNA-based polymerase chain reaction amplification and sequence-specific oligonucleotide probe hybridization methods to detect the presence and type of HPV and to detect allelic polymorphism in the HLA DRB1 and DQB1 loci. Results: Dysplasia cases were divided into two groups for comparison to controls: severe dysplasia/carcinoma in situ (CIS), and slight/moderate dysplasia. The frequency distribution of HLA class II haplotypes among the HPV16-positive severe dysplasia/CIS cases had a statistically significant (two-tailed P