Comparison of molecular changes in cervical intraepithelial neoplasia in HIV-positive and HIV-indeterminate subjects

Objective. HIV infection is associated with an increased incidence of cervi cal malignancy and its precursor lesions (CIN, cervical intraepithelial neo plasia) compared with the general population. We studied the molecular abno rmalities in the development of HIV-associated CIN and compared them with t hose present in CINs arising in HIV-indeterminate subjects ("sporadic CIN") . Methods. We investigated the presence of human papilloma virus (HPV) sequen ces, loss of heterozygosity (LOH), and microsatellite alterations (MAs) at five 3p chromosomal regions using 17 polymorphic markers in precisely micro dissected archival tissues from 16 HIV-positive CINs and compared them with those present in 39 sporadic CINs. Results. HPV sequences were detected in 36 of 55 (66%) CIN lesions, and hig h-risk oncogenic strains (HPV 16 and 18) accounted for 15 of them. No diffe rences in the HPV frequencies were found between HIV-associated and sporadi c CINs. Allelic losses at one or more chromosome 3p regions were frequently detected in CIN lesions (49%). The overall frequency of 3p LOH and the fre quencies at all individual regions were similar in HIV-associated and spora dic CINs. The frequency of MA present in the HIV-associated CIN cases (0.09 3) was sixfold greater than in sporadic CINs (0.01 1; P = 0.0001). At least 1 MA was present in 11 (69%) of 16 HIV-associated vs 5 of 39 (13%) sporadi c CIN (P = 0.0006). Molecular changes were independent of the presence of H PV sequences. Conclusion, Chromosome 3p deletions are frequently detected in the precurso r lesions of cervical carcinoma (CIN) and there are no differences in the 3 p LOH frequencies between HIV-associated and sporadic CIN lesions. Microsat ellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated GIN. Although the mechanism u nderlying the development of increased MAs is unknown, it may play a crucia l role in the development of many HIV-associated neoplasias. (C) 1999 Acade mic Press.