Regression of low-grade cervical intraepithelial neoplasia in patients with HLA-DRB1*13 genotype.
OBJECTIVE
The human leukocyte antigen (HLA)-DRB1*13 allele frequency is lower in women with cervical carcinoma than in the general population, suggesting that this allele could exert a protective effect against progression of cervical intraepithelial neoplasia (CIN) associated with human papillomaviruses (HPV). To test this hypothesis, we designed a prospective study of low-grade CIN (CIN1) and analyzed the probability of regression of these lesions according to HLA-DR and HPV status.


METHODS
The study sample was composed of 86 women with CIN1 who agreed to regular colposcopic follow-up and no immediate treatment. Biopsy specimens were taken under colposcopy for histology and for the determination of HPV and HLA status. Cases were classified into 3 groups: CIN1 regression, persistence for at least 12 months, or progression to CIN2 or 3.


RESULTS
The rate of spontaneous regression (95% confidence interval) at 24 months was 51.6% (39-61.6%) overall compared with 34.7% (13.4-50.8%) in HPV16/18 positive cases and 59.9% (43.7-71.4%) in HPV16/18-negative cases (P =.051). The rate of regression was 71.8% (40.8-86.5%) in patients with HLA-DRB1*13 and 45.9% (31.5-57.2%) in patients with other genotypes (P =.03). Regression reached 90.5% (38.9-98.5%) at 18 months in DRB1*13 patients with HPV16/18-negative-associated CIN (15.1% of the cases). In multivariable analysis, HLA-DRB1*13 allele and HPV16/18-negative status were independently associated with an increased probability for regression (adjusted hazard ratio 2.1 [1.0-4.1] and 2.5 [1.2-5.4], respectively).


CONCLUSIONS
A subset of approximately 15% of CIN1 highly likely to show spontaneous regression can be defined using 2 biologic parameters that characterize the viral causative agent and the host.


METHODS
II-2
Department of Pathology, Institut Curie, 26 rue d'Ulm, 75231 Paris Cedex, France. xavier.sastre@curie.net
Xavier
X
Sastre-Garau
Isabelle
I
Cartier
Nathalie
N
Jourdan-Da Silva
Patricia
P
De Crémoux
Virginia
V
Lepage
Dominique
D
Charron
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008875:Middle Aged; D009365:Neoplasm Regression, Spontaneous / Q000235:genetics; D027383:Papillomaviridae / Q000276:immunology* / Q000302:isolation & purification; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains