Investigation of dna repair capacity and genotoxic effects in human papillomavirus (HPV) positive individuals

VII. SUMMARYViral infections are important sources for human cancers. Approximately20% of all human cancers are thought to be caused by viruses. Cervical cancer is thesecond most frequent malignancy in women. Human papillomavirus (HPV) infection is themost common sexually transmitted disease in the world and the main cause of cervicalcancer. HPV DNA is detected approximately 80-90% of all cervical cancers and in 1995,IARC classified HPV 16 and 18 as human carcinogens (Group 1).This study was comprised of 31 HPV 16, 23 HPV 18 positive women and24 age-matched HPV negative healthy control individuals to identify the genotoxicity andDNA repair variability caused by HPV infection. HPV typings were detected by RT-PCR.Chromosomal aberration frequency and tail intensity% in HPV positivegroup and control group were not statistically different by chromosomal aberration andcomet techniques in peripheral blood lymphocytes (p>0,05), however, a statisticallysignificant increase in DNA damage (p<0,0001) was observed by comet assay in cervicalcells of HPV positive individuals? which is the target cell group for HPV infection.Challenge assay which is used as the biomarker of susceptibilitydemonstrated statistically significantly reduced DNA repair capacity in HPV positive groupas compared with the control group (p<0,0001). These results demonstrate that cervicalcells are much more sensitive than peripheral lymphocytes for detecting the HPV inducedDNA damage and comet assay can be used as a biomarker for detecting this damage.The difference in the DNA repair capacity in various exposures andinfections can be sensitively determined by Challenge assay which is one of thebiomarkers of susceptibility. This technique can be utilized clinically for identification ofcervical cancer susceptibility in HPV positive individuals.