Specific types of human papillomaviruses (HPV) are associated with most cases of pre-invasive and invasive neoplasia of the uterine cervix. HLA phenotype influences susceptibility and resistance to viral infections and may therefore influence the course of HPV-associated tumors. Some data suggest that specific HLA class-II alleles may be associated with protection from or susceptibility to papillomavirus-associated lesions, but these results are still controversial. Using molecular probes, we looked for associations between specific DQA1, DQB1, DRB1 HLA class-II alleles, HPV types and cervical cancer. The analysis was performed on a population of 126 patients with invasive cervical cancer. For HLA typing, 165 healthy individuals were taken as controls. The DRB1 1301/02 allele frequency significantly decreased in patients (11%) as compared to controls (29%). This difference in frequency was dependent on the HPV-positive status of tumors and was no longer significant in the group of HPV-negative lesions. The same trends were observed with the DRB1 1301/02-DQA1 0103-DQB1 0603 haplotype frequency. An increase in the frequency of the DRB1 1401/07 and DRB1 03 alleles was observed in patients under 40. Contrary to what has been reported in the literature, no increase in the DRB1 15 allele frequency was observed in our series and only a slight increase in the DQB1 03 frequency was found in patients (70%) compared to controls (58%). In our study, no positive correlations between cervical cancer in Frenchwomen and specific HLA DR-DQ haplotypes has been found. In contrast, a negative correlation between DRB1 1301/ 02 alleles and HPV-positive tumors has been observed. This may suggest a protective effect of DR13 against HPV-associated lesions of the cervix.