Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype

Clin Cancer Res. 2005 Jul 1;11(13):4717-23. doi: 10.1158/1078-0432.CCR-04-2599.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Cell Line, Tumor
  • Cohort Studies
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Genotype
  • HLA Antigens / genetics
  • HLA-A2 Antigen / genetics
  • Humans
  • K562 Cells
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / growth & development
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Prospective Studies
  • Remission, Spontaneous
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / pathology*
  • Uterine Cervical Dysplasia / virology

Substances

  • DNA, Viral
  • HLA Antigens
  • HLA-A2 Antigen