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Human Leukocyte Antigens I and II Haplotypes Associated With Human Papillomavirus 16-Positive Invasive Cervical Cancer in Mexican Women
  1. Dulce M. Hernández-Hernández, MD, PhD*,,
  2. Ricardo M. Cerda-Flores, PhD,
  3. Teresa Juárez-Cedillo, QFB, MSc*,,
  4. Julio Granados-Arriola, MD, MSc§,
  5. Gilberto Vargas-Alarcón, PhD,
  6. Teresa Apresa-García, RN*,,
  7. Isabel Alvarado-Cabrero, MD*,,
  8. Alejandro García-Carrancá, PhD,#,
  9. Mauricio Salcedo-Vargas, PhD*, and
  10. Alejandro Mohar-Betancourt, MD, PhD,#
  1. * Departments of Epidemiology, and
  2. Pathology, Medical Research Unit in Oncology Diseases, Epidemiological Research and Health Services Unit Oncology Hospital, Centro Medico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City;
  3. Population Genetics and Bioinformatics, Centro de Investigación Biomédicas del Noreste, Instituto Mexicano del Seguro Social, Monterrey;
  4. § Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán, Mexico City;
  5. Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City;
  6. Molecular Biology and Biotechnology, Instituto de Investigaciones Biomédica del Noreste, Universidad Nacional Autónoma de México, Mexico City; and
  7. # Cancer Biomedical Research Unit, Instituto Nacional de Cancerología, Mexico City, NM.
  1. Address correspondence and reprint requests to Dulce M. Hernández-Hernández, División de Epidemiología, Hospital de Oncología, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Av Cuauhtémoc 330, Col. Doctores, Delegación Cuauhtémoc, CP 06720 Mexico City, Federal District, NM. E-mail: dulcema{at}


Infection with human papillomavirus (HPV), mainly HPV type 16, is the major etiologic factor associated with cervical cancer (CC), but HPV infection alone is not sufficient for progression of precursor lesions. Host genetic susceptibility may lead to abnormal immune response resulting from virus persistence. Several studies have suggested a possible association with specific human leukocyte antigen (HLA) class I and II alleles and CC, but results are not consistent. The association of genetic HLA class I (A and B) and HLA class II (DR*B1 and DQ*B1) haplotypes with HPV16-positive CC (n = 104) and base population controls (n = 104) was evaluated in this Mexican population study. Sequence-specific primer HLA genes were determined by polymerase chain reaction (PCR)-based methods in peripheral blood cell counts (PCR sequence-specific oligonucleotides). The cervical swabs of 208 women were tested for HPV16 by Hybrid Capture II. Allele and haplotype HLA frequencies, Hardy-Weinberg tests, and a haplotype homogeneity test were estimated using the Arlequin software v. 3.01. Odds ratio (OR) was calculated to compare cases and control women. Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women. The HLA-A2-B44-DR4-DQ*0302, HLA-A24-B35-DR16-DQ*0301, and HLA-A2-B40-DR4-DQ*0302 haplotypes showed a positive association with CC (OR, >1), whereas HLA-A2-B39-DR4-DQ*0302, HLA-A24-B35-DR4-DQ*0302, and HLA-A68-B40-DR4-DQ*0302 showed a negative association (OR, <1). These results support the hypothesis that some HLA class I and II haplotypes could be involved with susceptibility for developing CC.

Abbreviations: Cervical Cancer-CC, confidence interval-CI, human leukocyte antigens-HLA, human papillomavirus-HPV, odds ratio-OR, polymerase chain reaction-PCR, relative risk-RR, relative light units-RLU, ribonucleic acid-RNA, sequence-sensitive oligonucleotide-SSO

  • Cervical cancer
  • Human leukocyte antigen
  • Human papillomavirus

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