This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trimble, C. L. Search for Related Content PubMed PubMed Citation Articles by Trimble, C. L.

Spontaneous Regression of High-Grade Cervical Dysplasia: Effects of Human Papillomavirus Type and HLA Phenotype

Authors' Affiliations: Departments of ¹ Gynecology and Obstetrics, ² Oncology, and ³ Pathology, Johns Hopkins Medical Institutions and ⁴ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

Requests for reprints: Cornelia L. Trimble, Department of Gynecology and Obstetrics, The Johns Hopkins Hospital, Phipps 255, 600 North Wolfe Street, Baltimore, MD 21287. Phone: 410-502-0512; Fax: 410-502-0621; E-mail: ctrimbl{at}jhmi.edu.

Purpose: Persistent infection with oncogenic human papillomaviruses (HPV) plays a central etiologic role in the development of squamous carcinomas of the cervix and their precursor lesions, cervical intraepithelial neoplasias (CIN). We carried out a prospective observational cohort study evaluating known, quantifiable prognostic variables of clinical behavior in women with high-grade cervical lesions.

Experimental Design: Our study cohort included healthy women with high-grade cervical lesions (CIN2/3) with residual visible lesions after colposcopically directed biopsy. We prospectively followed 100 women over 15 weeks before standard resection. HPV typing was done using PCR and a reverse line blot detection method.

Results: The rate of spontaneous histologic regression, defined as (CIN1 or less at resection) was 28%. The overall rate of HPV infection was 100%. HPV16 was identified in 68% of the lesions. Women with HPV16 only were significantly less likely to regress, compared with women with HPV types other than HPV16 (odds ratio, 0.342; 95% confidence interval, 0.117-0.997; P = 0.049). In the cohort with HPV16 only, patients who had an HLA*A201 allele had similar outcomes to those who did not carry A201. However, among patients with HPV types other than HPV16, the HLA*A201 allele interaction was significant; patients with HLA*A201 were the least likely to resolve.

Conclusions: CIN2/3 lesions associated with HPV16 alone are significantly less likely to resolve spontaneously than those caused by other types. Interactions among HPV type, HLA type, and regression rate support a role for HLA-restricted HPV-specific immune responses in determining disease outcome.

This article has been cited by other articles:

				Y. Zhai, R. Kuick, B. Nan, I. Ota, S. J. Weiss, C. L. Trimble, E. R. Fearon, and K. R. Cho Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion Cancer Res., November 1, 2007; 67(21): 10163 - 10172. [Abstract] [Full Text] [PDF]

				P. E. Gravitt, L. J. van Doorn, W. Quint, M. Schiffman, A. Hildesheim, A. G. Glass, B. B. Rush, J. Hellman, M. E. Sherman, R. D. Burk, et al. Human Papillomavirus (HPV) Genotyping Using Paired Exfoliated Cervicovaginal Cells and Paraffin-Embedded Tissues To Highlight Difficulties in Attributing HPV Types to Specific Lesions J. Clin. Microbiol., October 1, 2007; 45(10): 3245 - 3250. [Abstract] [Full Text] [PDF]

				J. K. Chan and J. S. Berek Impact of the Human Papilloma Vaccine on Cervical Cancer J. Clin. Oncol., July 10, 2007; 25(20): 2975 - 2982. [Abstract] [Full Text] [PDF]

				S. Peng, C. Trimble, L. Wu, D. Pardoll, R. Roden, C.-F. Hung, and T.-C. Wu HLA-DQB1*02-Restricted HPV-16 E7 Peptide-Specific CD4+ T-Cell Immune Responses Correlate with Regression of HPV-16-Associated High-Grade Squamous Intraepithelial Lesions Clin. Cancer Res., April 15, 2007; 13(8): 2479 - 2487. [Abstract] [Full Text] [PDF]

				J P A Baak, A-J Kruse, S J Robboy, E A M Janssen, B van Diermen, and I Skaland Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers J. Clin. Pathol., October 1, 2006; 59(10): 1017 - 1028. [Abstract] [Full Text] [PDF]