INTERPHASE CYTOGENETIC EVIDENCE FOR DISTINCT GENETIC PATHWAYS IN THE DEVELOPMENT OF SQUAMOUS NEOPLASIA OF THE UTERINE CERVIX

Human papillomavirus (HPV) infection has been implicated as an etiolog ic factor in most cervical cancers. However, additional genetic altera tions are thought to be required for the development of a carcinogenic genotype. In the present study, interphase cytogenetics utilizing per icentromeric probes specific for chromosomes 1, 3, 11, 17, 18, and X w as performed on paraffin-embedded tissue sections from 25 high-grade s quamous intraepithelial lesions (Sits) and 25 invasive squamous cell c arcinomas (ISCCs) of the cervix. HPV infection was determined by both in situ hybridization and broad-spectrum GP5+/GP6+ PCR. HPV was identi fied in all high-grade SILs (HPV 16, n = 16; 18, n = 2; 26, n = 1; 31, n = 4; 45, n = 1; 66, n = 1) and 23 (92%) ISCCs (HPV 16, n = 19; 18, n = 2; 31, n = 1, 39, n = 1). Aneusomy was identified in 11 (44%) high -grade SILs and 18 (72%) ISCCs. In 18 (62%) of these, relative under-r epresentation of chromosomes 3, 1 1, 17, and/or 18 was identified (8 h igh-grade SILs and 10 ISCCs). Tetrasomy of all six chromosomes was pre sent in two high-grade SILs but no ISCCs. Twelve (48%) high-grade SILs and seven (28%) ISCCs were disomic with all six chromosome probes, an d there was no relationship between HPV presence or type and chromosom e pattern. The presence of distinct patterns of numerical chromosome a bnormality in these lesions suggests that progression to high-grade SI L or invasive carcinoma can occur by more than one genetic pathway. Th e lack of correlation between chromosome pattern and HPV type indicate s that these pathways are not HPV type-specific. Whether these pattern s reflect differences in early gene expression, possibly related to vi ral integration, or differences in the biologic properties of HPV type variants remains to be established.