Genetic deletion and human papillomavirus infection in cervical cancer: Loss of heterozygosity sites at 3p and 5p are important genetic events

Abstract

'High-risk' human papillomavirus (HPV) types 16/18 are recognized as being associated with cervical cancer. We have already reported frequent loss of heterozygosity (LOH) at 3p, 3q, 4q, 5p and 5q in primary cervical cancer, the frequency at these sites ranging from 31.0 to 56.3%. The present analysis deals with these frequent-deletion sites in relation to HPV infection. HPV frequency, as determined by PCR and by Southern-blot, was 87.0%. Out of 45 HPV-positive tumours, 26 (57.8%) were 'high-risk' HPV-16/18-positive, with HPV type 16 predominant (24 of 26). Among these 24, 14 (58.3%) tumours had HPV-16 DNA integrated with the host genome. LOH on 3p revealed significant association with HPV-16/18 infection; 64.0% of LOH at 3p was in HPV16/18- positive tumours, vs. 23.3% in the tumours that did not reveal the presence of HPV16/18. On the other hand, 78.6% of LOH at 5p, which was the most frequent (56.3%), was in tumours without HPV16/18 infection, vs. 43.7% in tumours that had HPV16/18 infection, suggesting independence of HPV16/18 infection. At other sites, LOH did not differ, irrespective of the presence or absence of 'high-risk' HPV infection.