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Regression of Low-Grade Cervical Intraepithelial Neoplasia in Patients With HLA-DRB1*13 Genotype

Xavier Sastre-Garau, MD, PhD^*, Isabelle Cartier, MD, Nathalie Jourdan-Da Silva, MD, Patricia De Crémoux, MD, PhD, Virginia Lepage, MD^¶ and Dominique Charron, MD, PhD^¶

From the Departments of *Pathology, Biostatistics, and Physiopathology, Institut Curie; Laboratory of Dr. René Cartier; ¶Laboratory of Immunology and Institut National de la Santé et de la Recherche Médicale U396, Hôpital Saint-Louis, Paris, France.

Address reprint requests to: Xavier Sastre-Garau, MD, PhD, Laboratoire de Pathologie, Institut Curie, 26 rue d'Ulm, 75231, Paris Cedex, France; e-mail: xavier.sastre{at}curie.net.

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).

CONCLUSION: 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.

LEVEL OF EVIDENCE: II-2

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