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


METHODS
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.
Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. ctrimbi@jhmi.edu
Cornelia L
CL
Trimble
Steven
S
Piantadosi
Patti
P
Gravitt
Brigitte
B
Ronnett
Ellen
E
Pizer
Andrea
A
Elko
Barbara
B
Wilgus
William
W
Yutzy
Richard
R
Daniel
Keerti
K
Shah
Shiwen
S
Peng
Chienfu
C
Hung
Richard
R
Roden
Tzyy Choou
TC
Wu
Drew
D
Pardoll
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000254:growth & development; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology* / Q000821:virology; D011446:Prospective Studies; D012075:Remission, Spontaneous; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology* / Q000821:virology
D004279:DNA, Viral; D006680:HLA Antigens; D015789:HLA-A2 Antigen