Genetic abnormalities and HPV status in cervical and vulvar squamous cell carcinomas.
Cervical and vulvar cancers are diseases of the female lower genital tract, and high-risk human papillomavirus (HPV) infection is the most important risk factor for the development of both cancers. However, it is clear that additional genetic events are necessary for tumor progression, particularly in HPV-negative cases. We detected the presence of high-risk HPV16 and HPV18 genomes by gene-specific polymerase chain reaction and searched for common genetic imbalances by comparative genomic hybridization (CGH) in 28 cervical and 8 vulvar tumor samples and 7 cancer cell lines. The presence of the HPV genome was detected in 25/28 (89%) cervical tumors and 6/8 (75%) vulvar tumors. CGH of cervical and vulvar tumor samples revealed a consistent pattern of genetic changes in both cancers. Frequent gains were found in 1q, 3q, 5p, and 8q, and less consistent losses were detected in 2q, 3p, 4p, and 11p. Notably, a high-level amplification of 3q was found in 9/28 (32%) cervical tumors and 1/8 (12.5%) vulvar tumors, indicating a pivotal role of gain of 3q in cervical and vulvar carcinogenesis. Furthermore, gains of 5p identified in 9/28 (32%) cervical tumors and 3/8 (37.5%) vulvar tumors were seldom described, particularly in vulvar tumors. Our findings suggest that cervical and vulvar carcinomas bear similar chromosomal alteration hot spots that largely coincide with common genomic lesions during tumor progression, besides the initiation by infection and integration of oncogenic HPV.
Huang
Fung Yu
FY
Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 6/F, Professorial Block, Pokfulam Road, Hong Kong, China.
Kwok
Yvonne K Y
YK
Lau
Elizabeth T
ET
Tang
Mary H Y
MH
Ng
Tong Yow
TY
Ngan
Hextan Y S
HY
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D002869:Chromosome Aberrations; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000821:virology