CERVICAL-CANCER IN OLDER WOMEN - A MOLECULAR ANALYSIS OF HUMAN-PAPILLOMAVIRUS TYPES, HLA TYPES, AND P53 MUTATIONS

OBJECTIVE: The purpose of this study was to evaluate cervical cancers in older women to determine whether they differed from tumors in young er women with respect to human papillomavirus types, frequencies of p5 3 mutations, and presence of a proposed high-risk HLA-DR2 haplotype. S TUDY DESIGN: Cervical tissue was obtained from women undergoing surgic al treatment of in situ or invasive carcinoma of the cervix. Viral and genomic deoxyribonucleic acid was extracted. The presence of human pa pillomavirus deoxyribonucleic acid was detected by polymerase chain re action amplification. Viral subtypes were assigned by means of a combi nation of type-specific amplification and automated sequencing of the L1 region. The presence of p53 mutations was evaluated by direct seque ncing of exons 5 through 9. The HLA-DR locus was screened for the pres ence of the high-risk DRB11501 allele by means of selective polymeras e chain reaction amplification followed by agarose gel electrophoresis of HLA-DR2 types. RESULTS: Tumors from 39 women 62 to 85 years old we re analyzed. Tumors from 104 younger women formed a reference group. H uman papillomavirus 16 was found in 41% and 54% and human papillomavir us 18 was found in 10% and 12% of the tissue samples from older and yo unger women, respectively. The overall distributions of human papillom avirus types did not differ statistically between the groups. One of t he 25 older patients tested had a p53 mutation. This tumor also had a positive test result for human papillomavirus 18. The DR1501 allele w as present in 33% of the older patients and 28% of the younger patient s. The expected frequency of this allele in white Americans is 19.8%. The increased frequency of this allele among both older and younger wo men with cervical cancer was statistically significant (P < .05). CONC LUSIONS: We hypothesized that cervical cancer in older women might dif fer from that in younger women with respect to human papillomavirus ty pes, natural host immunity, or the frequency of nonviral origins of th e cancer. The findings show, however, that tumors from older women are extremely similar to those from younger women with respect to the hum an papillomavirus types present and the infrequent occurrence of p53 m utations. In addition we found that an HLA-DR allele that is associate d with a risk of cervical cancer in younger women is also associated w ith risk in older women. These findings are most consistent with a mod el similar to that in younger women but with an unusually long latency for the transforming effect of the virus in some hosts.