CERVICAL-CARCINOMA - HUMAN-PAPILLOMAVIRUS INFECTION AND HLA-ASSOCIATED RISK-FACTORS IN THE SPANISH POPULATION

There is evidence for a link between MHC and squamous cell carcinoma o f the cervix (SCCC), and different patterns of association in differen t patient cohorts have been reported. To investigate this subject in t he Spanish population, HLA class I, -II serotypings and HLA-DQB1 oligo genotypings of 142 patients and 138 healthy sex-age-matched controls w ere performed. Comparative analysis of the DR2-DQ3-stratified phenotyp es demonstrated a strong association between DR2 and DQ3 in SCCC (P-c9 < 7 x 10(-8)). However, no interaction was observed between the two H LA factors, which seem to confer two weak and independent risks. Thus, phenotypes with DR2 and/or DQ3 (patients, 79%, controls, 60%; P < 5 x 10(-4)) were over-represented, while the less common DR2/DQ3-negative phenotypes with the HLA class I A2 antigen were found to confer the h ighest risk (EF = 62%, P-c84 < 1 x 10(-2)) Of SCCC. Comparative analys is of allele frequencies revealed two weakly significant increases, on e for DQB10301 (P < 1 x 10(-2)) in low-moderate dysplasias (CINI,IT), and the other for DQB10402 (P < 3 x 10(-2)) in severe dysplasia in s itu (CINIII/CIS), and a trend for an increase of DQB1'0302 among CINI II/CIS and invasive SCCC (ISCCC). With regard to DQB1 genes encoding t he DR2-associated DQ serotypes, there was no significant deviation in patients. In contrast, the frequency of DQB10603 was found to be weak ly decreased in CINI,II (P < 5 x 10(-2)) and ISCCC (P < 3 x 10(-2)), i ndicating a protective effect for this DR13 serotype-associated allele . No significant association could be shown between HLA and HPV infect ive status. However, there is circumstantial evidence that HPV-infecte d lesions may have been misassigned in some cases, and the sample size was small, so a role for DQB alleles in modifying the course of HPV-i nduced diseases cannot be excluded. The observations in this study sug gest A2, DR2, DQB10301, DQB1*0402 and DQB1*0603 as independent factor s associated with SCCC and as relevant targets in HLA-restricted pepti de presentation. Our results are consistent with the theory that HLA l oci may have different contributions in susceptibility and resistance to low-moderate dysplasias, CIS and invasive SCCC.